Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modifications by atherosclerosis of endothelium-dependent and -independent relaxations were evaluated in carotid arteries isolated from Watanabe heritable hyperlipidemic (WHHL; age 20-29 months) and age-matched Japanese white (JW) rabbits. Marked, patchy atherosclerotic lesions were observed in all WHHL rabbit arteries. Endothelium-dependent relaxations induced by acetylcholine, partly depressed by N(G)-nitro-L-arginine (L-NA), were significantly inhibited in the WHHL rabbit arteries with atherosclerosis, compared with those in the arteries without atherosclerotic lesions from JW and WHHL rabbits. No difference was observed in the relaxation caused by superoxide dismutase in these arteries. Conversely, endothelium-dependent relaxations by substance P were greater in the arteries with and without atherosclerosis from WHHL rabbits than in the arteries from JW rabbits. Endothelium-independent relaxations elicited by sodium nitroprusside and 2,2-(hydroxynitrosohydrazino)bis-ethanamine (NOC18) did not differ in the arteries from JW and WHHL rabbits. The responses to acetylcholine and substance P of JW rabbit arteries with the endothelium were not attenuated by treatment with pertussis toxin. L-NA-resistant, endothelium-dependent relaxations by substance P were almost abolished by charybdotoxin, and atherosclerosis did not alter the response. It is concluded that endothelial functions, evaluated by substance P, in rabbit carotid arteries are not impaired by atherosclerosis and by long exposure to hyperlipidemia in vivo. Dysfunction of muscarinic receptors may be involved in the depressed response to acetylcholine. As far as the arteries used in the present study are concerned, responses mediated possibly by endothelium-derived hyperpolarizing factor (EDHF) are unlikely to be modulated by atherosclerosis.
 ...
PMID:Comparison of endothelium-dependent relaxation in carotid arteries from Japanese white and Watanabe heritable hyperlipidemic rabbits. 1106 23

Lipatrophic diabetes, also referred to as familial partial lipodystrophy, is a rare disease that is metabolically characterized by hypertriglyceridemia and insulin resistance. Affected patients typically present with regional loss of body fat and muscular hypertrophic appearance. Variable symptoms may comprise pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia, acanthosis nigricans, polycystic ovaria, and carpal tunnel syndrome. Mutations within the LMNA gene on chromosome 1q21.2 were recently reported to result in the phenotype of familial partial lipodystrophy. The genetic trait is autosomal dominant. We identified a family with partial lipodystrophy carrying the R482W (Arg(482)Trp) missense mutation within LMNA. Here we present the lipoprotein characteristics in this family in detail. Clinically, the loss of sc fat and muscular hypertrophy especially of the lower extremities started as early as in childhood. Acanthosis and severe hypertriglyceridemia developed later in life, followed by diabetes. The characterization of the lipoprotein subfractions revealed that affected children present with hyperlipidemia. The presence and severity of hyperlipidemia seem to be influenced by age, apolipoprotein E genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipemia is an early and prominent feature in the presented lipodystrophic family carrying the R482W mutation within LMNA.
 ...
PMID:Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene. 1134 41

The effect of L-arginine on the pattern of lipids and lipoproteins in normal and diabetic rats was studied. Three groups of 48 rats were studied during 12 days and compared with a control group (Group I, n = 5). Group I consisted of normal rats not treated with L-arginine. Group II. Normal rats treated with 10 mM L-arginine (i.p.). Group III. Diabetic rats (alloxan 120 mg/kg, i.p.) not treated (diabetic control). Group IV. Diabetic rats treated with 10 mM L-arginine (i.p.). The rats of each group were divided in subgroups of four each. Rats were anesthetized and blood was taken from aorta to determine glucose, triglycerides, cholesterol, total lipids, and low (LDL) and high density lipoproteins (HDL) and their corresponding apoproteins (Apo A-I and Apo B-100). We observed that the alloxan concentration used in this study reproduces the clinical manifestations of disease including hyperglycemia (from 132.5 +/- 7.6 to 544.3 +/- 16.9 mg/dL) in 96 h. As a consequence the levels of triglycerides, cholesterol, total lipids, and LDL and its apoprotein Apo B-100 were increased, whereas HDL and its apoprotein Apo A-I were diminished. The L-arginine injection tends to normalize the glycemia from 24 h; similarly, hyperlipidemia (triglycerides from 924.7 +/- 220.1 to 68.5 +/- 8.4 mg/dL, cholesterol from 107.7 +/- 0.6 to 64.5 +/- 4.2 mg/dL, LDL from 24.2 +/- 2.5 to 8.0 +/- 2.9 mg/dL) was also diminished. These results suggest that the beneficial effect of L-arginine administration on serum glucose values and lipid levels in diabetic rats can be mediated by polyamine formation, although the effect of L-arginine on insulin release as observed by other authors is not discarded.
 ...
PMID:Regulation of hyperglycemia and dyslipidemia by exogenous L-arginine in diabetic rats. 1136 55

Supraphysiological increases in serum triglycerides and cholesterol often occur during pregnancy, but their effects on vascular function are poorly understood. Intraperitoneal injection of the nontoxic surfactant poloxamer 407 (P-407) results in sustained elevation of triglycerides and cholesterol. We asked if P-407-induced hyperlipidemia during late pregnancy adversely affects mesenteric resistance artery vasodilator function. On days 13-15 of pregnancy, rats were given a single intraperitoneal injection of P-407, sterile water vehicle, or non-lipid-altering pluronic F-88 (P-88). Four days postinjection, serum triglycerides, cholesterol, free fatty acids, and the lipid peroxidation product malondialdehyde were significantly increased in P-407-treated rats. Mesenteric arteries from P-407-treated rats displayed significant increases in myogenic reactivity (constrictor responses to step increases in intraluminal pressure). The nitric oxide (NO) blocker N(alpha)-methyl-L-arginine increased the myogenic response in control but not in P-407 arteries, normalizing group differences. Endothelial removal increased myogenic reactivity beyond that of prior NO synthase inhibition in controls and potentiated myogenic reactivity in P-407 arteries such that responses again converged. Relaxation responses to the endothelium-dependent vasodilator methacholine did not differ. We conclude that that P-407-induced hyperlipidemia during pregnancy increases myogenic reactivity due to selective attenuation of an NO-mediated vasodilator component of the myogenic response.
 ...
PMID:Endothelial function and myogenic reactivity in small mesenteric arteries of hyperlipidemic pregnant rats. 1155 43

According to contemporary views, the endothelium is not only a barrier separating blood from surrounding tissues, but a dynamic, heterogeneous organ, which possesses many secretory, metabolic and immunologic functions. Endothelial cells produce mediators, which regulate blood flow, influence platelet adhesion and aggregation, coagulation and fibrinolysis and also immunological response. Endothelial dysfunction is defined as an imbalance between vascular relaxing and contracting factors, between procoagulant and anticoagulant mediators or growth-inhibiting and growth-promoting substances. The definition is often confined to dysfunction of the vessel wall tonus control. The endothelial dysfunction frequently proceeds structural changes in vessels, as e.g. atherosclerotic plaque formation, neointima formation and vessel wall remodelling. This dysfunction has been confirmed in systemic hypertension, atherosclerosis, cardiac syndrome X, heart failure, using various invasive and non-invasive techniques. There are pharmacologic and non-pharmacologic methods to modify endothelial functions. It is obligatory to reduce risk factors of atherosclerosis, which lead to endothelial cell damage, i.e. hypertension, hyperlipidemia, cigarette smoking, estrogen deficiency and elevated levels of homocysteine. The role of physical exercise, low-cholesterol diet, discontinuation of smoking is emphasised. Among drugs statins, angiotensin-converting enzyme inhibitors and hormone replacement therapy are considered particularly beneficial. The importance of angiotensin receptor antagonists, endothelin receptor antagonists, L-arginine, growth factors and calcium-channel blockers for the improvement of endothelial function is studied.
 ...
PMID:[Vascular endothelium--function, disorders and clinical modification probes]. 1171 25

We examined three missense polymorphisms of platelet-endothelial cell adhesion molecule-1 (PECAM-1), Val125Leu, Asn563Ser, and Gly670Arg, in 136 Japanese patients with myocardial infarction and 235 healthy Japanese controls. We found that these polymorphisms were in linkage disequilibrium with each other and that frequencies of 125Leu, 563Ser, and 670Arg alleles were significantly increased in patients compared with controls (0.522 vs 0.447, p = 0.048; 0.585 vs 0.502, p = 0.030; and 0.577 vs 0.492, p = 0.032, respectively). The frequencies of homozygotes for 563Ser and 670Arg alleles were also significantly increased in the patients (33.1% vs 23.4%, odds risk [OR] = 1.62, p = 0.040, 95% confidence interval [95%CI] = 1.01-2.58; and 32.4% vs 23.0%, OR = 1.60, p = 0.048, 95%CI = 1.00-2.57, respectively). These observations suggest that the 563Ser/Ser genotype and 670Arg/Arg genotype of PECAM-1 are novel genetic risk factors of myocardial infarction in Japanese. Stratification analysis of the patients showed that the associations of these PECAM-1 genotypes with myocardial infarction were preferentially found in male and younger patients (age of onset of myocardial infarction less than 60 years). In addition, the associations were stronger in patients with three-vessel disease than in the others and appeared independent of conventional risk factors including smoking, hypertension, diabetes mellitus, hyperlipidemia, and obesity.
 ...
PMID:Polymorphisms in the platelet-endothelial cell adhesion molecule-1 (PECAM-1) gene, Asn563Ser and Gly670Arg, associated with myocardial infarction in the Japanese. 1179 74

Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and abnormal lipoprotein profiles similar to those in type III hyperlipoproteinemia. Recently, these conditions have been shown to be associated with some apolipoprotein E (apoE) mutations. We found an apoE mutation (designated apoE-Sendai) that substitutes arginine 145 with proline. This mutation occurs most frequently in Japanese patients with LPG. To elucidate the etiological role of this mutation in the apoE gene, we established an experimental model for LPG by transducing apoE-Sendai in apoE knockout mice with the use of an adenovirus vector. Based on the findings in patients with LPG and its animal model, we suggest that the glomerular lesions are not only caused by hyperlipidemia, but also by in situ interaction between lipoprotein-containing mutant apoE with the glomerulus. In this review, we outline the clinical features of LPG and discuss the relationship between apoE mutations and LPG.
 ...
PMID:Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy. 1185 53

Effect of coconut protein in rats fed high fat cholesterol containing diet on the metabolism of lipids and lipid peroxides was studied. In addition, effect of coconut protein were compared with rats fed L-arginine. The results indicate that those fed coconut protein and those fed L-arginine showed significantly lower levels of total cholesterol, LDL+ VLDL cholesterol, Triglycerides and Phospholipids in the serum and higher levels of serum HDL cholesterol. The concentration of total cholesterol, triglycerides and phospholipids in the tissues were lower in these groups. There was increased hepatic cholesterogenesis which is evident from the higher rate of incorporation of labeled acetate into free cholesterol. Increased conversion of cholesterol to bile acids and increased fecal excretion of bile acids were observed. Feeding coconut protein results in decreased levels of Malondialdehyde in the heart and increased activity of Superoxide dismutase and Catalase. Supplementation of coconut protein causes increased excretion of urinary nitrate which implies higher rate of conversion of arginine into nitric oxide. In the present study, the arginine supplemented group and the coconut protein fed group produced similar effects. These studies clearly demonstrate that coconut protein is able to reduce hyperlipidemia and peroxidative effect induced by high fat cholesterol containing diet and these effects are mainly mediated by the L-arginine present in it.
 ...
PMID:Hypolipidemic and antiperoxidative effect of coconut protein in hypercholesterolemic rats. 1188 11

Common complications of diabetes are accelerated atherosclerosis and vascular disturbances. We investigated whether the simultaneous insult of hyperlipemia-hyperglycemia affects the reactivity of the resistance arteries to bradykinin (BK), and if so, what are the mechanisms responsible for this disturbance. Experiments were conducted on male Golden Syrian hamsters rendered hyperlipemic (H) by a fat-rich diet, diabetic (D) by streptozotocin injection, or simultaneously hyperlipemic-diabetic (HD). Normal age-matched animals were used as controls (C). At 24 weeks after the induction of disease(s) the vascular reactivity of the mesenteric resistance arteries to BK (10(-8)-10(-4) M) was assayed by the myograph technique. To explore the role of nitric oxide (NO) in modulating the endothelium-dependent BK-induced relaxation, two experimental approaches were employed: (i) in vivo administration of L-arginine (622.14 mg/kg bw) to H, D, and HD hamsters (for 12 weeks); (ii) in vitro blockage of nitric oxide synthase by N(omega)-nitro- L-arginine methyl ester (10(-4) M). To evaluate the contribution of Ca2+-activated K+ channel(s) to BK-induced relaxation, the resistance arteries were exposed to 10(-3) M tetraethylammonium. Comparatively, the endothelium-independent relaxation was assayed using sodium nitroprusside (10(-8)-10(-4) M). The results showed that compared to the H and D groups, the HD hamsters exhibited the most reduced vasodilation of the resistance arteries to BK (34.09 +/- 1.5%). The diminished vasodilation was found to be due to a dual mechanism: an L-arginine:NO pathway and a NO-independent process, mediated via Ca2+-activated K+ channels. In vivo administration of L-arginine had favourable effects especially in the HD group, which manifested (i) an; 30% improvement of attenuated BK relaxation, (ii) an increase in sensitivity of the response to BK, (iii) a 3-fold diminishment of plasma hyperglycemia. Collectively, these data explain in part, the mechanisms and possible ways to correct the arterial endothelial dysfunction when diabetes is complicated with hyperlipemia.
 ...
PMID:Mechanisms of decreased bradykinin- induced vasodilation in experimental hyperlipemia-hyperglycemia: contribution of nitric oxide and Ca2+-activated K+ channels. 1190 2

The objective of this study was to evaluate whether administration of L-arginine, the substrate for nitric oxide synthesis, was able to ameliorate the endothelial dysfunction and the morphological changes induced by the combined insult of hyperlipemia and hyperglycemia. To this purpose, golden Syrian hamsters were rendered simultaneously hyperlipemic and diabetic (HD group) for 24 weeks, and then orally treated with 622.14 mg/kg per day L-arginine, for 12 weeks (HD + L-arg group). The following assays were carried out: (1) spectrophotometric: concentrations of circulating glucose, cholesterol, and creatinine, the activity of angiotensin-converting enzyme (ACE), and the osmotic fragility of erythrocyte plasmalemma; (2) myographic: the endothelium-dependent and -independent relaxation of the resistance arteries (i.d. 210-250 microm) to 10(-8) to 10(-4) M acetylcholine (ACh) or sodium nitroprusside (SNP); and (3) electron-microscopic: the ultrastructure of the resistance arteries, myocardium, and kidney glomeruli, which are main targets of hypertensive complications. The results showed that oral supplementation with L-arginine in simultaneous hyperlipemia-hyperglycemia induced in hamsters had favorable effects on: (1) homeostasis, i.e., diminished the concentration of circulating glucose (by ~63%) and cholesterol (by approximately 10%), reduced the ACE activity (by approximately 45%), and lowered the osmotic fragility of erythrocyte plasmalemma (as marker for the oxidative stress in plasma); (2) mesenteric resistance arteries, which showed (in 10(-4) M ACh) an improved endothelium-dependent relaxation (72.40+/-4.6% in the HD + L-arg group vs 61.90+/-1.45% in the HD group) and a reduced thickness (approximately 1.32-fold) of the smooth muscle cells' extracellular matrix; and (3) the heart, which displayed approximately 16% diminishing of the thickness of the left ventricular wall, and an apparently normal structure of the myocardium; the restoration of the thickness of the pericapillary extracellular matrix to almost normal dimensions was also observed. Administration of L-arginine did not modify the high level of plasma creatinine determined for the HD group (approximately 48% increased vs control group) and had no effect on the thickened, nodular basal lamina of the kidney capillaries. The results indicate that endothelial dysfunction established in combined hyperlipemia-diabetes is distinctive for each vascular bed (mesenteric arterioles, heart capillaries, kidney glomerular capillaries), and there is a reversible stage of the dysfunction in which L-arginine oral supplementation induced beneficial effects.
 ...
PMID:Beneficial effects of L-arginine supplementation in experimental hyperlipemia-hyperglycemia in the hamster. 1201 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>